Norepinephrine transporter and Dopamine transporter (NET (for norepinephrine transporter), DAT (for dopamine transporter))

The norepinephrine transporter (NET) and dopamine transporter (DAT) are closely related members of the neurotransmitter:sodium symporter family, functioning as integral membrane proteins that regulate the reuptake of norepinephrine and dopamine, respectively, from the synaptic cleft into presynaptic neurons. NET (gene: SLC6A2) and DAT (gene: SLC6A3) both have twelve transmembrane domains and are essential for terminating neurotransmitter signaling and maintaining homeostasis in the central nervous system. Both are established targets for approved psychiatric and neurological drugs, as well as drugs of abuse. While structurally homologous, they differ in substrate specificity and brain distribution. Both are considered key therapeutic targets in neuropsychiatric and neurodegenerative conditions, as well as in the context of addiction pharmacotherapy.

Other names

Norepinephrine transporter: NETNoradrenaline transporterSLC6A2Dopamine transporter: DATSLC6A3

Inhibition of norepinephrine or dopamine reuptake, increasing synaptic concentrations of these neurotransmitters. Competitive inhibition at the transporter (e.g., TCAs, atomoxetine, bupropion block NET/DAT). Substrate competition (e.g., amphetamines induce reverse transport, causing efflux of neurotransmitter).